Sphingolipid Metabolism Perturbations in Rett Syndrome
Department of Translational Medicine, Federico II University, 80131 Naples, Italy
Telethon Institute of Genetics and Medicine, Pozzuoli, 80078 Naples, Italy
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Authors to whom correspondence should be addressed.
Present address: PerkinElmer Genetics, Pittsburgh, PA 15275, USA.
Metabolites 2019, 9(10), 221; https://doi.org/10.3390/metabo9100221
Received: 12 September 2019 / Revised: 4 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the MECP2 gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features of Rett syndrome. We performed a semi-quantitative tandem mass spectrometry-based analysis that measured over 900 metabolites on blood samples from 14 female subjects with Rett syndrome carrying MECP2 mutations. The metabolic profiling revealed alterations in lipids, mostly involved in sphingolipid metabolism, and sphinganine/sphingosine, that are known to have a neurotrophic role. Further investigations are required to understand the mechanisms underlying such perturbations and their significance in the disease pathogenesis. Nevertheless, these metabolites are attractive for studies on the disease pathogenesis and as potential disease biomarkers.